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Immunocontraception of mammalian wildlife: ecological and immunogenetic issues

Desmond W Cooper and Elisabeth Larsen Australian and Conservation Laboratories, School of Biological, Earth and Environmental Sciences, The University of New South Wales, Sydney, New South Wales 2052, Correspondence should be addressed to D W Cooper; Email: [email protected]

Abstract involves stimulating immune responses against or reproductive hormones thus preventing conception. The method is being developed for the humane control of pest and overabundant populations of mammalian wildlife. This paper examines three fundamental issues associated with its use: (1) the difficulties of obtaining responses to self-, (2) the likely evolution of genetically based non-response to immunocontraceptive agents, and (3) the possible changes in the array of pathogens possessed by the target species after generations of immunocontraception. Our review of the literature demonstrates that the barriers to an effective immunocontraceptive are at present very basic. Should they be overcome, the effects of immunocontraception on the immunogenetic constitution of wildlife populations through the selection for non- responders must be examined. We suggest that the attempt to use the animal’s own to modulate may be incompatible with the basic biological function of protection against infectious disease. Research programs on mammalian immunocontraception should involve measurement of the heritability of non-response and an assessment of the likely change in the response of the contracepted population to possible pathogens. Reproduction (2006) 132 821–828

Introduction future (Rao 2001, Aitken 2002). Women’s health advocates have objected to all forms of immunocon- The regulation of human and animal population traception because of perceived health risks and the numbers constitutes a difficult and largely unsolved potential for political abuse of the (Richter contemporary problem. In the developed world, steroid 1994). Human male immunocontraceptives have contraceptives for humans are both widely used and received much less attention and do not appear to be efficacious. Elsewhere they are too costly. The develop- feasible in the near future (Delves et al. 2002). ment of less expensive methods is considered necessary Immunocontraceptives for wild animals have a (Aitken et al. 1993). One such method is immunocon- different objective than those for humans. Their main traception, i.e. the vaccination against , eggs, or aim is to check population growth rather than to reproductive hormones to prevent either fertilization or contracept particular individuals. If some animals are the production of gametes. Attempts to design human irreversibly sterilized so much the better whereas such immunocontraception have a long history (Joshi 1973, an effect in human medicine would be ethically most Stevens 1975, Basten 1988, Gupta & Talwar 1994). The undesirable. Immunocontraceptives for animals are targets include sperm antigens, oocyte antigens, ostensibly humane and could potentially be used on especially (PZP), gonadotropin the large scale required for wildlife population riboflavin carrier , gonadotropins and gonado- regulation. Research progress to date has been reviewed tropin releasing hormones (Delves et al. 2002). The most in Tyndale-Biscoe (1991, 1994), Barber & Fayrer-Hosken advanced method involves immunization against human (2000), Barlow (2000), and Cooper & Herbert (2001). chorionic gonadotropin, in reality a method of very early Three fundamental questions remain to be addressed: (1) pregnancy termination (Baird 2000). It now seems likely Can sufficiently strong immune responses be provoked that problems associated with and against the antigens (immunogens) of gametes or variability of response will prevent any widespread use reproductive hormones to cause contraception in a of immunocontraception in humans in the foreseeable proportion of animals large enough for effective

q 2006 Society for Reproduction and DOI: 10.1530/REP-06-0037 ISSN 1470–1626 (paper) 1741–7899 (online) Online version via www.reproduction-online.org Downloaded from Bioscientifica.com at 09/28/2021 06:24:58AM via free access 822 D W Cooper and E Larsen population management? (2) How rapidly will variation immunizations were boosted at least once (see Table 2). in these responses lead to the evolution of failure to The need for multiple injections and the dependence respond to the immunocontraceptive agent? (3) What upon adjuvant to achieve the necessary level of response will be the ecological consequences of the likely renders the whole approach impractical at present. The changes to the immunogenetic constitution of the most commonly used adjuvant, Freund’s Adjuvant, also population as a result of selection for non-responders? induces a range of undesirable side effects and its use is In particular, will the endemic pathogens of the species being challenged on animal welfare grounds (Leenaars change? There is considerable information which allows et al. 1994, 1998). There is at present no feasible or us to answer at least in part the first two questions. The acceptable method of promoting responses to self- third is of fundamental importance but even a antigens sufficient to cause immunocontraception. preliminary answer is not possible at present. Jackson et al. (2001) attempted to overcome the problem of lack of to self-antigens in the absence of adjuvant by inserting the cytokine Target species interleukin-4 into mousepox with the intention of Population control of native and exotic is increasing the humoral response. The virus was then generally justified by environmental degradation, inserted into the mice with the unwelcome outcome that competition with and predation on native wildlife, the mice all died very quickly. This work caused alarm conflicts with humans over food production, potential because of the possibility that this technology could lead spread of pathogenic infectious diseases and the to a method for simple conversion of relatively possibility of population crashes of over-abundant fauna innocuous into lethal ones, which could be or of wildlife populations near urban areas. Although still used in biological warfare (Finkel 2001). in its infancy, immunocontraception is regarded as being Another possible problem with virus-vectored more humane than the traditional methods of wildlife immunocontraception is the potential for the hori- population control, such as shooting, trapping, zontal transfer of the immunocontraceptive gene into poisoning, or pathogenic agents and its use has strong viruses affecting other species (Becker 2000). While it support from influential animal welfare agencies world- may be possible to create genetically modified wide (Oogjes 1997, Grandy & Rutberg 2002). Table 1 lists organisms without adverse effects on the target mammalian species for which immunocontraception is animals, the effects they might have on related species being investigated and for which the method could be they come in contact with make any use of this applied. In all these species, there are at present no approach questionable. completely efficacious, cost-effective, or socially accep- table methods for population regulation available. Variation in response and genetic change Variation in response to biocontrol agents is a widespread Immune responses to self-antigens phenomenon. This variation has frequently led to Responses to self-antigens are unusual and mainly weak. evolution of a degree of resistance so that the agent is no This constitutes a major barrier to the development of an longer useful. The evolution of resistance to insecticides immunocontraceptive. Table 2 summarizes data on hasbeenreviewedbyMcKenzie (1996). He draws a attempts to induce immunocontraception using a variety distinction between biocontrol agents with responses of antigens in 14 mammalian species. The data in Table 2 within the phenotypic range and those with responses show that in most cases a significant proportion of the outside the phenotypic range of the target species. An population is not contracepted by administration of the agent which initially kills all members of the target species immunocontraceptive . The reason for this could is acting outside the normal phenotypical range, while one be either genetic or environmental. In either case it which kills onlya fraction of the population is acting within indicates that a fraction of the population will continue to the normal phenotypical range. He points out that when breed despite the administration of the contraceptive. In resistance appears in the former case it is frequently most cases, there is likely to be at least in part genetic monogenic, while in the latter case a number of different causes underlying lack of response. If so, the genes for genetic regions are involved, i.e. it is probably multi- lack of response will be selected for and in a compara- factorial. The basic genetic parameter to be estimated in tively small number of generations most of the population either case is heritability, i.e. the extent to which genetic will be non-responsive. This implies that the immuno- variation is controlled by genetic as opposed to environ- contraceptive can be useful for only a short period of time. mental factors. The relative fertility of the immunocon- All studies summarized in Table 2 involve the use of tracepted animals in Table 2 is O10% in 27 out of the 32 some kind of adjuvant, i.e. a substance or array of data sets. A proportion of non-responders is characteristic substances designed to enhance the immune response. of most species. Only three species (, There are no reports of successful immunocontraception Fallow deer and Norway rat) out of 14 had no non- without some form of adjuvant. Moreover, most responders (Table 2). Following McKenzie’s (1996)

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Table 1 Immunocontraception: target species and justification for fertility control.

Management Population Species Location issues control needs References K-selected species Koala Australia; local Habitat degradation; likely destruc- Control methods with public Martin & Handasyde overpopulations tion of own habitat; highly regarded acceptance (1999) species Southern Africa Habitat degradation; public safety Control methods with public Hanks (2001) and health concerns; highly acceptance regarded species Wild USA, Australia Habitat degradation; conflicts with Control methods with public Berger (1986), Dobbie , timber and mining indus- acceptance et al. (1993), Furbish & try interests (USA); highly regarded Albano (1994) species White-tailed deer USA Habitat degradation; public safety Control methods with public McShea et al. (1997), and health concerns; high frequen- acceptance Warren (1997) cies of deer-vehicle collisions; crop and garden damage Feral donkey/Burro USA, Australia, Habitat degradation; public safety Broad-scale control over large, McCool (1981), Berger Africa and health concerns; highly remote and inaccessible areas (1986), Freeland & regarded species (Australia) Choquenot (1990) Brushtail possum New Zealand; Habitat degradation (New Zealand); Broad-scale control over large, often Montague (2000) major introduced public, livestock and wildlife health inaccessible, areas (New Zealand). pest species concerns; reservoir for bovine Alternative to poison baits (1080) tuberculosis Macropods Australia Public, livestock and wildlife health Control methods with public Dawson (1995), Pople & concerns; high frequencies of kan- acceptance Grigg (1999) garoo-vehicle collisions; highly regarded species European red fox Australia; major Predation on native wildlife Control over continental area Saunders et al. (1995) introduced pest (Australia); public, livestock and (Australia). Alternative to poison species wildlife health concerns baits (1080) Pinnipeds Worldwide Possible contribution to the Contraception suggested as humane Butterworth et al. depletion of fish stocks alternative to culling (1988), Brown et al. (1996), Mohn & Bowen (1996) Feral cat Worldwide; Predation on native wildlife Control over continental area Newsome (1991), major introduced (Australia); public and wildlife (Australia) Alternative to poison baits Bomford et al. (1996), pest species in health concerns (1080) Mahlow & Slater (1996) Australia Feral dog Worldwide Public and livestock safety and Control methods with public Fleming et al. (2001), health concerns; predation on native acceptance Sabeta et al. (2003) wildlife (Australia) Feral pig Worldwide; Habitat degradation; damage to Control methods with public Choquenot et al. (1996) major introduced economic resources; public, live- acceptance pest species in stock and wildlife health concerns Australia Badger UK Public, livestock and wildlife health Control methods with public Krebs et al. (1998), concerns; reservoir for bovine acceptance Donnelly et al. (2003) tuberculosis Grey squirrel UK; introduced Habitat degradation; threat to the Control methods with public Moore et al. (1997) species native Red squirrel acceptance r-selected species European rabbit Worldwide; Habitat degradation; major cost to Broad-scale control over large areas Lawson (1995), major vertebrate agriculture; public, livestock and Williams et al. (1995) pest species in wildlife health concerns Australia Rodents Worldwide Major damage to economic Broad-scale control over large areas. Caughley et al. (1998), resources, incl. crops, pastures, Species-specific alternatives to Chambers et al. (1999), stored grain, livestock, buildings and rodenticides Seamark (2001) infrastructure; public, livestock and wildlife health concerns argument, this implies that non-response is likely to be will increase in any one of these populations under the multi-factorial in genetic terms. There are no data which selective influence of immunocontraception. However, will allow estimates of the heritability of non-response to some idea of the likely change per generation given the immunocontraception in any of the species in Table 2.We initial frequency of non-responders can be found using are unable to predict the rate at which this characteristic Falconer’s (1965) model for threshold characters (Table 3). www.reproduction-online.org Reproduction (2006) 132 821–828

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Table 2 Relative fertility of immunocontracepted females in 14 mammalian species.

Reproductive Reduction No. of performance Statistical in relative Species Immunogen Adjuvant immunizations (control, treated) significancea fertility (%)b Reference C ! LDH-C4 CGP11637 emulsi- 3 Offspring/females P 0.02 62 O’Hern et al. promiscuous fied w. Squale- 10/13, 4/14 (1997) ne:Arlacel -A (4:1) Brushtail possum Whole sperm Freund’s complete 3 Offspring/females P!0.001 83 Duckworth (FCA), Freund’s 12/16, 2/16 et al. (1998) incomplete (FIA) in boosters Tammar wallaby Porcine ZP FCA, FIA in boosters 5 Offspring/females P!0.05 (nZ6) 100 Kitchener et al. 4/6, 0/6 (2002) African elephant First schedule Porcine ZP Adjuvant used, type 3 Offspring/females PZ0.005 50 Fayrer-Hosken not given 16/18, 8/18 et al. (2000) Second schedule Porcine ZP Adjuvant not 2 Offspring/females PZ0.001 77 Fayrer-Hosken mentioned 2/10 (no true et al. (2000) control) Wild horse Porcine ZP FCA, FIA in boosters 3–4 Pregnancy rate Not stated 85 Kirkpatrick 3/6, 1/14 et al. (1991) White-tailed deer First schedule Porcine ZP FCA, FIA in booster 2 Fawns/doe years P!0.0001 87 Miller et al. 30/16, 4/16 (2000a) Second schedule RC55 FCA, FIA in booster 2 Fawns/doe years P!0.05 28 Miller et al. 30/16, 19/14 (2000a) Third schedule RC75a FCA, FIA in booster 2 Fawns/doe years P!0.01 27 Miller et al. 30/16, 11/8 (2000a) Fourth schedule Combined FCA, FIA in booster 2 Fawns/doe years PO0.05 0 Miller et al. antigens 30/16, 16/8 (2000a) White-tailed deer KLH-GnRH FCA, FIA in boosters 2–4 Fawns/doe years P!0.01 89 Miller et al. 35/19, 5/24 (2000b) White-tailed deer Porcine ZP FCA, FIA in boosters 2–3 Fawns/doe years P!0.01 76 Miller et al. 35/19, 25/57 (2000c) White-tailed deer First schedule GnRH FCA, FIA in boosters 3 Fawns/doe years P!0.0005 75 Curtis et al. 110/90, 36/118 (2002) Second schedule Porcine ZP FCA, FIA in boosters 3 Fawns/doe years P!0.0005 87 Curtis et al. 72/56, 10/60 (2002) Fallow deer SpayVac FCA 1 Pregnancy rate P!0.0001 100 Fraker et al. 322/334, 0/22 (2002) Burro Porcine ZP FCA, FIA in boosters 2–3 Offspring/females P!0.05 88 Turner et al. 6/11, 1/16 (1996) Grey seal SIZP (SpayVac) FCA 1 Pups/female 2.76, P!0.001 92 Brown et al. 0.22 (1996, 1997) Tule elk Porcine ZP FCA, FIA in boosters 3–4 Calves/cow years Not stated 91 Shideler et al. 53/91, 5/104 (2002) Cat Porcine ZP FCA, FIA in boosters 5 Pregnancy rate Not stated 50 Ivanova et al. 2/2, 1/5 (1995) Cat First schedule SpayVac FCA 1 Mean litter size PZ0.8859 13 Gorman et al. 5.2, 4.5 (2002) Second schedule SpayVac Alum 1 Mean litter size PZ0.8859 15 Gorman et al. 5.2, 4.4 (2002) European rabbit Myxoma vec- FCA, FIA in boosters 3 Mean litter size Not stated 5 Kerr et al. tored ZPB 7.4, 7.0 (1999) Norway rat First schedule MZPP/KLH FCA, FIA in boosters 3 Pregnancy rate PO0.05 40 Miller et al. 7/8, 4/8 (1997) Second schedule GnRH/KLH FCA, FIA in boosters 3 Pregnancy rate P!0.004 100 Miller et al. 7/8, 0/8 (1997) Wild mouse KLH-mZP3 FCA, FIA in boosters 5 Pregnancy rate PZ0.046 56 Hardy et al. 8/15, 7/30 (2002b) BALB/c mouse First schedule Murine rFA-1 FCA, FIA in boosters 4 Mean litter size P!0.0001 64 Naz & Zhu (71–81 days) 8.9, 3.2 (1998) Second schedule Murine rFA-1 FCA, FIA in boosters 4 Mean litter size PO0.05 0 Naz & Zhu (283 days) 8.6, 9 (1998) BALB/c mouse First schedule sp56FLAG FCA, FIA in boosters 6 Offspring/females PZ0017 39 Hardy & 55/14, 12/5 Mobbs (1999)

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Table 2 Continued.

Reproductive Reduction No. of performance Statistical in relative Species Immunogen Adjuvant immunizations (control, treated) significancea fertility (%)b Reference Second schedule sp56FLAG FCA, FIA in boosters 4 Offspring/females Not stated 3 Hardy & 55/14, 19/5 Mobbs (1999) BALB/c mouse First schedule MBP-polyepi- FCA, FIA in boosters 4 Mean litter size Not stated 37 Hardy et al. tope A 5.2, 3.3 (2002a) Second schedule MBP-polyepi- FCA, FIA in boosters 4 Mean litter size P!0.05 60 Hardy et al. tope B 5.2, 2.1 (2002a) Third schedule 6XHis-polye- FCA, FIA in boosters 4 Mean litter size Not stated 3 Hardy et al. pitope A 6.5, 6.3 (2002a)

Investigations have been conducted on approximately 70 species. This table includes only true experiments, i.e. studies with an immunized group compared with a control group. aThe P values are those given in the references cited. bRelative fertility is defined as the mean no. of offspring for females in the vaccinated group divided by the same figure for the control group (i.e. unimmunized females).

Reproduction is a good example of a threshold character; it Delves & Roitt (2005) review attempts to immunocon- is an all-or-none attribute which can be affected by a tracept mammals and conclude that GnRH is the most variety of underlying genetic and environmental factors. If promising target, because of its evolutionary conserved heritabilities are high, rapid selection occurs. This is shown sequence. by the high percentage of non-responders that occur within one generation (Table 3). A limited place for immunocontraception in wildlife Immunogenetic issues management could be in species with long generation Infectious diseases are assumed to be one of the main times. Genetic changes in them, if they occur, will take classes of selective forces which act upon genes decades. Claims have been made for the potential controlling immune responses (Klein et al. 1993). efficacy of immunocontraception for African elephants Immunocontraceptive agents also have the potential to (Fayrer-Hosken et al. 2000, Delsink et al. 2002), influence the genetic constitution of a population with although this view has been challenged on demographic respect to the ability to mount immune responses. The grounds (Pimm & van Aarde 2001). Long-term studies on two are similar in that pathogens which cause plagues and immunocontraception in wild report 78–94.2% immunocontraceptive agents are both capable of exert- contraceptive efficacy (Kirkpatrick et al. 1995, Turner ing very strong selective pressure with the potential for et al. 1997, 2002, Turner & Kirkpatrick 2002). rapid genetic change. However, they differ in two Zoo animals are convenient for immunocontraception important respects. First, most pathogens are cellular studies of wild species, because of their long-term and antigenically more complex than most immunocon- accessibility, although the small numbers usually traceptive agents, which consist of one or a few proteins available make controls hard to find. This is illustrated and in some cases associated carbohydrate. Second, they by an investigation involving 27 females from 10 felid have opposite directions of selection; resistance to a species. Immunization with PZP and Freund’s Complete pathogen involves a positive response, whereas resist- Adjuvant gave several kinds of adverse reaction but no ance to an immunocontraceptive involves non-response. convincing evidence of an effect upon fertility The consequences of this kind of selection imposed by an (Harrenstien et al. 2004). immunocontraceptive agent require study. It seems likely that it will alter the immunogenetic constitution of the Table 3 Predicted proportion of non-responder daughters after one target species. The existence of genes governing response generation of selection by immunocontraception of mothers given various heritabilities (after Falconer 1965). to pathogens is well documented in humans for malaria (Hill 2001), tuberculosis (Blackwell 1998, Bellamy Heritability (%) 2003), and HIV (McNicholl & Cuenco 1999, Carrington Non-responder & O’Brien 2003). Relevant examples are found in New mothers (%) 100 80 60 50 Zealand Red Deer in which susceptibility to tuberculosis has high heritability (Mackintosh et al. 2000) and in the 5 1511108 10 23 19 16 15 NRAMP1 association with the human response to leishmaniasis (Bucheton et al. 2003). The complexities The prediction has been arrived at by entering the table in Falconer of the co-evolution of pathogens and hosts and its (1965) which relates heritability for a threshold trait to incidences in parent and offspring. The response to selection (predicted percentage of biomedical significance are beginning to be unraveled non-responders) obtained has been halved because selection is being (Woolhouse et al. 2002). Both experimental (Lively & carried out on one sex. Dybdahl 2000) and theoretical analyses (e.g. Nowak www.reproduction-online.org Reproduction (2006) 132 821–828

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& May 1994) point to the inherent difficulties of incompatible with the basic biological function of prediction of the course of these interactions. Prediction resisting pathogens. We have not discussed some of and detection of the ecopathological consequences of the the practical issues. For example, all fertility control use of immunocontraception of wild animals will also be methods have the problem of delivery of the control made difficult by the spread of emerging infectious agent. Highly valued animals must be treated without diseases as a result of human activity (Daszak et al. 2000). harming them. When this is the case, fertility control The effect of immunocontraception upon genetic methods with fewer concomitant problems, such as diversity could be significant. There is the possibility surgical sterilization or the use of steroids or gonado- that restriction of breeding to a small group of animals tropin-based hormones, would be competitive with which are closely related will result in localized immunocontraception (Cooper & Herbert 2001). inbreeding. This will be especially likely if their capacity to resist the immunocontraceptive is the result of shared uncommon genotype. Acevedo-Whitehouse et al. Acknowledgements (2003) have shown that in California sea lions, inbreeding is associated with a wide range of diseases. We acknowledge helpful comments from , Tony They suggest that inbred individuals could act dispro- Basten, Kathy Belov, David Briscoe, Bryce Buddle, Margaret Carrington, Charles Daugherty, Dick Frankham, Cathy portionally as reservoirs of infectious agents. Herbert, John McKenzie, Bill Sherwin, Jim Shields, Roger Selection based upon immune responses could be on one Short, and Kyall Zenger. Our research on population control in of two parts of the genome: the MHC (major histocompat- koalas and kangaroos is supported by the Australian Research ability complex) region which governs responses to specific Council grant LPO560344. The authors declare that there is immunogens, or other genes, e.g. NRAMP which govern no conflict of interest that would prejudice the impartiality of the functioning of the immune system in general (Bellamy this scientific work. 1999). The tightly linked MHC genes and the resultant linkage disequilibrium mean that selection on one gene will result in changes in gene frequencies at other loci. This could either raise or lower susceptibility to other pathogens. References Understanding of the non-MHC genetic component of Acevedo-Whitehouse K, Gulland F, Denise G & Amos W 2003 variability of the immune response is much less advanced Inbreeding: disease susceptibility in California sea lions. Nature than for the MHC component. This understanding is needed 422 35. to attempt any predictions concerning immunocontracep- Aitken RJ 2002 Immunocontraceptive for human use. tion-based selection. Journal of Reproductive Immunology 57 273–287. Aitken RJ, Paterson M & Koothan PT 1993 Contraceptive vaccines. Experimental approaches to this question have until British Medical Bulletin 49 88–99. now been very difficult. The existence of genetic maps of Baird DT 2000 Overview of advances in contraception. British Medical some wild animals (e.g. Tammar wallaby (Zenger et al. Bulletin 56 704–716. 2002)) may now allow a genomic approach, in which Barber MR & Fayrer-Hosken RA 2000 Possible mechanisms of whole genome DNA typing may allow the identification mammalian immunocontraception. Journal of Reproductive Immu- nology 46 103–124. of changes in gene frequency which accompany the Barlow ND 2000 The ecological challenge of immunocontraception: application of immunocontraception or a pathogen, editor’s introduction. Journal of Applied 37 897–902. through comparing treated and control populations. A Basten A 1988 vaccines. Baillie`re’s Clinical Immunology concomitant survey of pathogens in the two groups may and Allergy 2 759–774. Becker Y 2000 Evolution of viruses by acquisition of cellular RNA or identify susceptibility regions, whose existence could be DNA nucleotide sequences and genes: an introduction. Virus Genes further tested in lab-based investigation. The genome 21 7–12. would thus be assayed for these genes, and test the extent Bellamy R 1999 The natural resistance-associated macrophage protein to which the same genes are involved in responses to and susceptibility to intracellular pathogens. Microbes and Infection different pathogens and to immunocontraception. 1 23–27. Bellamy R 2003 Susceptibility to mycobacterial infections: the A good model system to address these questions is importance of host genetics. Genes and Immunity 4 4–11. wildlife tuberculosis which is of economic significance in Berger J 1986 Wild Horses of the Great Basin: Social Competition and several countries, e.g. Britain (Delahay et al. 2002), New Population Size, Chicago: University of Chicago Press. Zealand (Buddle et al. 2002), and the United States (Palmer Blackwell JM 1998 Genetics of host resistance and susceptibility to et al. 2002). Considerable information on the genetic intramacrophage pathogens: a study of multicase families of tuberculosis, leprosy and leishmaniasis in north-eastern Brazil. control of response to mycobacterial antigens is available International Journal for Parasitology 28 21–28. (North & Medina 1998, Kramnik et al. 2000, Bellamy Bomford M, Newsome A & O’Brien P 1996 Solutions to feral animal 2003). The possibility of obtaining results relevant to problems: ecological and economic principles. In Conserving human mycobacterial susceptibility may also encourage Biodiversity: Threats and Solutions, pp 202–209. Eds RA Bradstock, DA Keith, RT Kingsford, D Lunney & DP Sivertsen. Sydney: Surrey use of this system. Beatty and Sons. We conclude that attempting to use the immuno- Brown RG, Kimmins WC, Mezei M, Parsons JL, Phoajdak B & logical system to modulate reproduction could be Bowen WD 1996 Birth control for grey seals. Nature 379 30–31.

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Brown RG, Bowen WD, Eddington JD, Kimmins WC, Mezei M, Fleming PL, Corbett L, Harden R & Thomson P 2001 Managing the Parsons JL & Pohajdak B 1997 Evidence for a long-lasting single Impacts of Dingoes and Other Wild Dogs, Canberra: Bureau of Rural administration contraceptive vaccine in wild grey seals. Journal of Sciences. Reproductive Immunology 35 43–51. Fraker MA, Brown RG, Gaunt GE, Kerr JA & Pohajdak B 2002 Long- Bucheton B, Abel L, Kheir MM, Mirgani A, El-Safi SH, Chevillard C & lasting, single-dose immunocontraception of feral fallow deer in Dessein A 2003 Genetic control of visceral leishmaniasis in a British Columbia. Journal of Wildlife Management 66 1141–1147. Sudanese population: candidate gene testing indicates a linkage to Freeland WJ & Choquenot D 1990 Determinants of herbivore carrying the NRAMP1 region. Genes and Immunity 4 104–109. capacity: plants, nutrients and Equus asinus in Northern Australia. Buddle BM, Skinner MA, Wedlock DN, Collins DM & de Lisle GW Ecology 71 589–597. 2002 New generation vaccines and delivery systems for control of Furbish CE & Albano M 1994 Selective herbivory and plant community bovine tuberculosis in and wildlife. Veterinary Immunology structure in a mid-Atlantic salt marsh. Ecology 75 1015–1022. and Immunopathology 87 177–185. Gorman SF, Levy JK, Hampton AL, Collante WR, Harris AL & Butterworth DS, Duffy DC, Best PB & Bergh MO 1988 On the Brown RG 2002 Evaluation of a porcine zona pellucida vaccine scientific basis for reducing the South African seal population. South for the immunocontraception of domestic kittens (Felis catus). African Journal of Science 84 179–188. Theriogenology 58 135–149. Grandy JW & Rutberg AT 2002 An animal welfare view of wildlife Carrington M & O’Brien SJ 2003 The influence of HLA genotype on contraception. Reproduction (Cambridge, ) Supplement 60 AIDS. Annual Review of Medicine 54 535–551. 1–7. Caughley J, Bomford M, Parker B, Sinclair R, Griffiths J & Kelly D 1998 Gupta SK & Talwar GP 1994 Contraceptive vaccines. Advances in Managing Vertebrate Pests: Rodents, Canberra: Bureau for Rural Contraceptive Delivery Systems 10 255–265. Sciences. Hanks J 2001 Conservation strategies for Africa’s large mammals. Chambers LK, Lawson MA & Hinds LA 1999 Biological control of Reproduction, Fertility, and Development 13 459–468. rodents – the case for fertility control using immunocontracep- Hardy CM & Mobbs KJ 1999 Expression of recombinant mouse sperm tion, Ecologically-Based Management of Rodent Pests, Canberra: protein sp56 and assessment of its potential for use as an antigen in Australian Centre for International Agricultural Research. an immunocontraceptive vaccine. Molecular Reproduction and Choquenot D, McIlroy J & Korn T 1996 Managing Vertebrate Pests: Development 52 216–224. Feral Pigs, Canberra: Bureau of Rural Sciences. Hardy CM, Pekin J & ten Have JF 2002a Mouse-specific immunocon- Cooper DW & Herbert CA 2001 Genetics, biotechnology and traceptive polyepitope vaccines. Reproduction (Cambridge, England) population management of over-abundant mammalian wildlife in Supplement 60 19–30. Australasia. Reproduction, Fertility, and Development 13 451–458. Hardy CM, ten Have JF, Mobbs KJ & Hinds LA 2002b Assessment of the Curtis PD, Pooler RL, Richmond ME, Miller LA, Mattfeld GF & immunocontraceptive effect of a zona pellucida 3 antigen in Quimby FW 2002 Comparative effects of GnRH and porcine zona wild mice. Reproduction, Fertility, and Development 14 151–155. pellucida (PZP) immunocontraceptive vaccines for controlling Harrenstien LA, Munson L, Chassy LM, Liu IK & Kirkpatrick JF 2004 reproduction in white-tailed deer (Odocoileus virginianus). Repro- Effects of porcine zona pellucida immunocontraceptives in zoo duction (Cambridge, England) Supplement 60 131–141. felids. Journal of Zoo and Wildlife Medicine 35 271–279. Daszak P, Cunningham AA & Hyatt AC 2000 Emerging infectious Hill AV 2001 The genomics and genetics of human infectious disease diseases of wildlife–threats to biodiversity and human health. susceptibility. Annual Review of Genomics and Human Genetics 2 Science 287 443–449. 373–400. Dawson TJ 1995 Kangaroo: Biology of the Largest Marsupial, Sydney: Ivanova M, Petrov M, Klissourska D & Mollova M 1995 Contraceptive University of New South Wales Press. potential of procine zona pellucida in cats. Theriogenology 43 Delahay RJ, De Leeuw AN, Barlow AM, Clifton-Hadley RS & 969–981. Cheeseman CL 2002 The status of Mycobacterium bovis infection Jackson RJ, Ramsay AJ, Christensen CD, Beaton S, Hall DF & Ramshaw IA in UK wild mammals: a review. Veterinary Journal 164 90–105. 2001 Expression of mouse interleukin-4 by a recombinant ectromelia Delsink AK, van Altena JJ, Kirkpatrick J, Grobler D & Fayrer-Hosken RA virus suppresses cytolytic responses and overcomes 2002 Field applications of immunocontraception in African genetic resistance to mousepox. Journal of Virology 75 1205–1210. elephants (Loxodonta africana). Journal of Reproduction and Joshi SH 1973 An immunological approach to fertility control. Fertility. Supplement 60 117–124. American Journal of Pharmacy 145 22–26. Delves PJ & Roitt IM 2005 Vaccines for the control of reproduction- Kerr PJ, Jackson RJ, Robinson AJ, Swan J, Silvers L, French N, Clarke H, status in mammals and aspects of comparative interest. Develop- Hall DF & Holland MK 1999 in female rabbits (Oryctolagus cuniculus) alloimmunized with the rabbit zona pellucida protein ZPB ments in Biologicals 121 265–273. either as a purified recombinant protein or expressed by recombinant Delves PJ, Lund T & Roitt IM 2002 Antifertility vaccines. Trends in myxoma virus. Biology of Reproduction 61 606–613. Immunology 23 213–219. Kirkpatrick JF, Liu IKM, Turner JW & Bernoco M 1991 Antigen recognition Dobbie WR, Berman DMK & Braysher ML 1993 Managing Vertebrate in feral mares previously immunized with porcine zonae pellucidae. Pests: Feral Horses, Canberra: Bureau of Resource Sciences. Journal of Reproduction and Fertility. Supplement 44 321–325. Donnelly CA, Woodroffe R, Cox DR, Bourne J, Gettinby G, Le Fevre AM, Kirkpatrick JF, Naugle R, Liu IKM & Turner JW 1995 Effects of Seven McInerney JP & Morrison WI 2003 Impact of localized badger culling Consecutive Years of Porcine Zonae Pellucidae Contraception on on tuberculosis incidence in British cattle. Nature 426 834–837. Ovarian Function in Feral Mares, Biology of Reproduction Duckworth JA, Buddle BM & Scobie S 1998 Fertility of brushtail Monograph Series. vol 1, pp 411–413 (Equine Reproduction VI). possums (Trichosurus vulpecula) immunised against sperm. Kitchener AL, Edds LM, Molinia FC & Kay DJ 2002 Porcine zonae Journal of Reproductive Immunology 37 125–138. pellucidae immunization of tammar wallabies (Macropus eugenii): Falconer DS 1965 The inheritance of liability to certain diseases, fertility and immune responses. Reproduction, Fertility, and Develop- estimated from the incidence among relatives. Annals of Human ment 14 215–223. Genetics 29 51–76. Klein J, Satta Y, O’HUigin C & Takahata N 1993 The molecular descent Fayrer-Hosken RA, Grobler D, Van Altena JJ, Bertschinger HJ & of the major histocompatibility complex. Annual Review of Kirkpatrick JF 2000 Immunocontraception of African elephants. Immunology 11 269–295. Nature 407 149. Kramnik I, Dietrich WF, Demant P & Bloom BR 2000 Genetic control Finkel E 2001 Australia. Engineered mouse virus spurs bioweapon of resistance to experimental infection with virulent Mycobacterium fears. Science 291 585. tuberculosis. PNAS 97 8560–8565. www.reproduction-online.org Reproduction (2006) 132 821–828

Downloaded from Bioscientifica.com at 09/28/2021 06:24:58AM via free access 828 D W Cooper and E Larsen

Krebs JR, Anderson RM, Clutton-Brock T, Donnelly CA, Frost S, O’Hern PA, Liang ZG, Bambra CS & Goldberg E 1997 Colinear Morrison WI, Woodroffe R & Young D 1998 Badgers and bovine TB: synthesis of an antigen-specific B- epitope with a ‘promiscuous’ conflicts between conservation and health. Science 279 817–818. tetanus toxin T-cell epitope: a synthetic peptide immunocontracep- Lawson M 1995 Rabbit virus threatens ecology after leaping the fence. tive. Vaccine 15 1761–1766. Nature 378 531. Oogjes G 1997 Ethical aspects and dilemmas of fertility control of Leenaars PP, Hendriksen CF, Angulo AF, Koedam MA & Claassen E unwanted wildlife: an animal welfarist’s perspective. Reproduction, 1994 Evaluation of several adjuvants as alternatives to the use of Fertility, and Development 9 163–167. Freund’s adjuvant in rabbits. Veterinary Immunology and Immuno- Palmer MV, Waters WR & Whipple DL 2002 Milk containing pathology 40 225–241. Mycobacterium bovis as a source of infection for white-tailed deer Leenaars PP, Koedam MA, Wester PW, Baumans V, Claassen E & fawns (Odocoileus virginianus). Tuberculosis (Edinburgh, Scotland) Hendriksen CF 1998 Assessment of side effects induced by injection 82 161–165. of different adjuvant/antigen combinations in rabbits and mice. Pimm SL & van Aarde RJ 2001 Population control: African elephants Laboratory Animals 32 387–406. and contraception. Nature 411 766. Lively CM & Dybdahl MF 2000 Parasite adaptation to locally common Pople T & Grigg G 1999 Commercial Harvesting of Kangaroos in host genotypes. Nature 405 679–681. Australia, Canberra: Environment Australia. Mackintosh CG, Qureshi T, Waldrup K, Labes RE, Dodds KG & Rao AJ 2001 Is there a role for contraceptive vaccines in fertility Griffin JF 2000 Genetic resistance to experimental infection with control?. Journal of Biosciences 26 425–427. Mycobacterium bovis in red deer (Cervus elaphus). Infection and Richter J 1994 Anti-fertility ‘vaccines’: a plea for an open debate on the Immunity 68 1620–1625. prospects of research. Newsletter (Women’s Global Network on Mahlow JC & Slater MR 1996 Current issues in the control of stray and Reproductive Rights) 46 3–5. feral cats. Journal of the American Veterinary Medical Association Sabeta CT, Bingham J & Nel LH 2003 Molecular epidemiology of canid 209 2016–2020. rabies in Zimbabwe and . Virus Research 91 203–211. Martin R & Handasyde K 1999 The Koala: Natural History, Saunders GR, Coman B, Kinnear J & Braysher M 1995 Managing Conservation and Management, Sydney: University of New South Vertebrate Pests: Foxes, Canberra: Bureau of Rural Science. Wales Press Ltd. Seamark RF 2001 Biotech prospects for the control of introduced McCool CJ 1981 Feral Donkeys in the Northern Territory: Report to the mammals in Australia. Reproduction, Fertility, and Development 13 Feral Animals Committee of a Working Party on the Feral Donkey 705–711. Problem, Darwin: Department of Primary Production. Shideler SE, Stoops MA, Gee NA, Howell JA & Lasley BL 2002 Use of McKenzie JA 1996 Ecological and Evolutionary Aspects of Insecticide porcine zona pellucida (PZP) vaccine as a contraceptive agent in Resistance, Texas, USA: Academic Press/R.G. Landes. free-ranging tule elk (Cervus elaphus nannodes). Reproduction McNicholl JM & Cuenco KT 1999 Host genes and infectious diseases. (Cambridge, England) Supplement 60 169–176. HIV, other pathogens, and a public health perspective. American Stevens VC 1975 Potential control of fertility in women by Journal of Preventive Medicine 16 141–154. immunization with HCG. Research in Reproduction 1–2. McShea WJ, Underwood HB & Rappole JH 1997 The Science of Turner A & Kirkpatrick JF 2002 Effects of immunocontraception on Overabundance: Deer Ecology and Population Management, population, longevity and body condition in wild mares (Equus Washington, D.C.: Smithsonian Institution Press. caballus). Reproduction (Cambridge, England) Supplement 60 Miller LA, Johns BE, Elias DJ & Crane KA 1997 Comparative efficacy of 187–195. two immunocontraceptive vaccines. Vaccine 15 1858–1862. Turner JW, Liu IKM & Kirkpatrick JF 1996 Remotely delivered Miller LA, Johns BE & Killian GJ 2000a Immunocontraception of white- immunocontraception in free-roaming feral burros (Equus asinus). tailed deer using native and recombinant zona pellucida vaccines. Journal of Reproduction and Fertility 107 31–35. Animal Reproduction Science 63 187–195. Turner JW, Liu IKM, Rutberg AT & Kirkpatrick JF 1997 Immunocon- Miller LA, Johns BE & Killian GJ 2000b Immunocontraception of white- traception limits foal production in free-roaming feral horses in tailed deer with GnRH vaccine. American Journal of Reproductive Nevada. Journal of Wildlife Management 107 31–35. Immunology 44 266–274. Turner JW, Liu IKM, Flanagan DR, Bynum KS & Rutberg AT 2002 Miller LA, Johns BE & Killian GJ 2000c Long-term effects of PZP Porcine zona pellucida (PZP) immunocontraception of wild horses immunization on reproduction in white-tailed deer. Vaccine 18 (Equus caballus) in Nevada: a 10 year study. Reproduction 568–574. (Cambridge, England) Supplement 60 177–186. Mohn R & Bowen WD 1996 Grey seal predation on the Eastern Scotian Tyndale-Biscoe CH 1991 Fertility control in wildlife. Reproduction, Shelf: modeling the impact on Atlantic cod. Canadian Journal of Fertility, and Development 3 339–343. Fisheries and Aquatic Sciences 53 2722–2738. Tyndale-Biscoe CH 1994 Virus-vectored immunocontraception of feral Montague TLe 2000 The Brushtail Possum: Biology, Impact and mammals. Reproduction, Fertility, and Development 6 281–287. Management of an Introduced Marsupial, Lincoln, NZ: Manaaki Warren RJ 1997 The challenge of deer overabundance in the 21st Whenua Press. century. Wildlife Society Bulletin 25 213–214. Moore HD, Jenkins NM & Wong C 1997 Immunocontraception in Williams K, Parer I, Coman B, Burley J & Braysher M 1995 Managing rodents: a review of the development of a sperm-based immuno- Vertebrate Pests: Rabbits, Canberra: Bureau of Rural Science. contraceptive vaccine for the grey squirrel (Sciurus carolinensis). Woolhouse ME, Webster JP, Domingo E, Charlesworth B & Levin BR Reproduction, Fertility, and Development 9 125–129. 2002 Biological and biomedical implications of the co-evolution of Naz RK & Zhu X 1998 Recombinant fertilization antigen-1 causes a pathogens and their hosts. Nature Genetics 32 569–577. contraceptive effect in actively immunized mice. Biology of Zenger KR, McKenzie LM & Cooper DW 2002 The first comprehensive Reproduction 59 1095–1100. genetic linkage map of a marsupial: the tammar wallaby (Macropus Newsome AE 1991 Feral cats: an overview. In The Impact of Cats on eugenii). Genetics 162 321–330. Native Wildlife, Ed. C Potter. Canberra: Australian National Parks and Wildlife Service. North RJ & Medina E 1998 How important is Nramp1 in tuberculosis?. Received 21 May 2006 Trends in Microbiology 6 441–443. Nowak MA & May RM 1994 Superinfection and the evolution of First decision 22 June 2006 parasite virulence. Proceedings of the Royal Society of London. Revised manuscript received 30 July 2006 Series B 255 81–89. Accepted 10 October 2006

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